PT  - JOURNAL ARTICLE
AU  - Josephe A. Honorat
AU  - Lars Komorowski
AU  - Keith A. Josephs
AU  - Kai Fechner
AU  - Erik K. St Louis
AU  - Shannon R. Hinson
AU  - Sabine Lederer
AU  - Neeraj Kumar
AU  - Avi Gadoth
AU  - Vanda A. Lennon
AU  - Sean J. Pittock
AU  - Andrew McKeon
TI  - IgLON5 antibody
AID  - 10.1212/NXI.0000000000000385
DP  - 2017 Sep 01
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e385
VI  - 4
IP  - 5
4099  - http://nn.neurology.org/content/4/5/e385.short
4100  - http://nn.neurology.org/content/4/5/e385.full
SO  - Neurol Neuroimmunol Neuroinflamm2017 Sep 01; 4
AB  - Objective: To describe the phenotypes, treatment response, and outcome of IgLON5 autoimmunity.Methods: Archived serum and CSF specimens from 367 patients known to harbor unclassified antibodies which stained neural synapses diffusely (mimicking amphiphysin-IgG) were reevaluated by indirect immunofluorescence assay (IFA) using a composite of mouse tissues and recombinant IgLON5-transfected cell-based assay (CBA, Euroimmun).Results: Available specimens (serum, 25; CSF, 9) from 26/367 patients (7%) had identical IFA appearance and robust IgLON5 CBA positivity. Clinical information was available for 20/26 patients; 13 were women. Median disease-onset age was 62 years (range, 46–75 years). Most patients had insidious onset and progression of neurological symptoms affecting movement and sleep predominantly. Sleep disorders were sleep-disordered breathing (11) and parasomnias (3). Brainstem disorders were gait instability (14), dysphagia (10), abnormal eye movements (7), respiratory dysfunction (6), ataxia (5), craniocervical dystonia (3), and dysarthria (3). Findings compatible with hyperexcitability included myoclonus (3), cramps (3), fasciculations (2), and exaggerated startle (2). Neuropsychiatric disorders included cognitive dysfunction (6), psychiatric symptoms (5), and seizures (1). Dysautonomia, in 9, affected bladder function (7), gastrointestinal motility (3), thermoregulation (3), and orthostatic tolerance (1). Just 2 patients had coexisting autoimmune disease. Brain MRI findings were nonspecific and CSF was noninflammatory in all tested. Seven of 9 immunotherapy-treated patients improved: 6 of those 7 were stable at last follow-up. Three untreated patients died. Each IgLON5-IgG subclass (1–4) was readily detectable in ≥80% of specimens using CBA.Conclusions: IgLON5-IgG is diagnostic of a potentially treatable neurological disorder, where autoimmune clues are otherwise lacking.AHI=Apnea-Hypopnea Index; ANNA=antineuronal nuclear antibody; CBA=cell-based assay; GAD65=glutamic acid decarboxylase 65; MSA=multiple system atrophy; OSA=obstructive sleep apnea; PSP=progressive supranuclear palsy